The main cause of death in cystic fibrosis (CF) patients is progressive pulmonary insufficiency frequently associated with chronic infections of the respiratory tract by Pseudomonas aeruginosa. Bacteria of this species synthesize numerous extracellular products contributing to its pathogenicity. An alginate-like exopolysaccharide is characteristic for mucoid mutants predominating among P. aeruginosa isolates from CF patients. It interferes with immune defense mechanisms of the host and probably protects the bacteria against certain antibiotics. Furthermore, it is involved in the formation of bacterial microcolonies that resist mucociliary clearance, opsonisation, and phagocytosis. Exotoxin A and elastase are regarded as the most important among various extracellular enzymes involved in pulmonary injury in CF patients. Exotoxin A inhibits eukaryotic protein synthesis leading to necrosis; elastase, together with other Pseudomonas-proteases, induces hemorrhagic lesions and necrosis and seems to inactivate immunoglobulins and complement factors. Phospholipase C and glycolipid represent two hemolysins of P. aeruginosa that may contribute to cytopathogenic effects in infected lungs. No primary defect in the immunological defense mechanisms of CF patients has been described so far. Antibodies against various P. aeruginosa antigens including those mentioned above have been demonstrated, but a complete elimination of the bacteria from infected lungs has not been observed. Therapy of pulmonary P. aeruginosa infections in CF patients usually includes combinations of antibiotics of the beta-lactam and aminoglycoside type. Difficulties arise from an unusually high intrinsic resistance of P. aeruginosa as well as from poor penetration of many antibiotics into the sputum of CF patients. Therefore, future efforts to manage the Pseudomonas problem in CF will probably concentrate on prophylactic therapy, e.g. childhood vaccination of CF patients in order to prevent bacterial colonization of the respiratory tract.